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Modifiable
Hypertension
Dyslipidemia
Diabetes
Atrial fibrillation
SCD
Goldstein L, et al. Circulation. 2001;103:163-182.
Broderick J, et al. Stroke. 1998;29:415-421.
Brown WV. Clin Cornerstone. 2004;6(suppl 3):S30-S34.
TIA/prior stroke
Carotid stenosis
Cigarette smoking Obesity
Physical inactivity
HRT
Potentially Modifiable
Metabolic syndrome
Excess alcohol
Drug abuse
OCPs
Sleep-disordered breathing
Migraine
Hyperhomocysteinemia
Lipoprotein (a)
Hypercoagulability
Inflammation
Infection
Diabetes and Stroke Prevention
• Kenyan prevalence of DM 3.9% (2-12%)
• The prevalence of diabetes in persons with stroke is about 15-33%.
• DM a risk factor for stroke, but relationship to recurrent stroke unclear.
• DM is a clear RF in lacunar strokes
Diabetes Mellitus BP Control Class I A
ACEI/ARB Class I A
Statin, especially in those with additional risk
factors
Class I A
Fibrate Class IIb B
Addition of a fibrate to a statin in DM is not useful
for decreasing stroke risk.
Class III B
Aspirin Class IIb B
Blood lipids and Stroke Prevention
Modest relationship between elevated total cholesterol or LDL with increased risk of ischemic stroke
Higher serum triglycerides linked to ischemic stroke and large artery atherosclerosis
Link between LDL and ICH
Meta-analysis: the larger the reduction in LDL-C the larger the reduction in stroke
SPARCL – Stroke Prevention by Aggressive Reduction in Cholesterol Levels
4371 persons with LDL-C = 2.6-4.9 mmol/L
Randomized to 80 mg atorvastatin vs. placebo
Endpoint: fatal and nonfatal stroke = 11.2% vs. 13.1%
5 yr absolute RR, 2.2%, HR 0.84; 85% CI (0.71 to 0.99;
P=0.03)
5 yr absolute RR in cardiovascular events was 3.5%
(HR, 0.80; 95% CI, 0.69-0.92; P=0.002).
Recommendations/targets ↑LDL, ↓HDL
N Engl J Med. 2006;355(6):549
Dyslipidemia
Statins Class I A
Fibric acid derivatives Class IIb C
Niacin Class IIb C
Bile acid sequestrants
Ezetimibe
Class IIb C
Atrial Fibrillation Screening
CHADS2VASc
HASBLED
Class IIa B
• Warfarin
• Dabigatran (RE-LY)
• Rivaroxaban (ROCKET AF)
Class I A
Class I B
Aspirin Class I A
High-risk patients with AF unsuitable for
anticoagulation→→→ Clopidogrel + Aspirin
Class IIb B
• Asymptomatic Carotid Stenosis
• OCPs
• Sickle Cell disease
• TCD screening
• Transfusion
• Hydroxyurea
• BMT
• Other Stroke risks
Primary Stroke prevention
• Diet and nutrition
• Physical inactivity
• Obesity and body fat distribution
• Alcohol consumption
• Cigarette smoking
Primary Stroke prevention
Hyperhomocysteinemia
B-complex vitamins,
pyridoxine (B6 ), Cobalamin
(B12 ) and folic acid
effectiveness not well
established
IIb; B
Elevated Lipoprotein (a)
Niacin IIb; B
Hypercoagulability
Role of screening IIb;C
Specific treatments for primary
stroke prevention in asymptomatic
patients
IIb;C
Low-dose aspirin not indicated for
primary stroke prevention in
persons who are persistently aPL
positive.
III;B
Inflammation and Infection
hs-CRP or Lp-PLA2 ~↑ risk of stroke IIb B
Chronic inflammatory disease RA /SLE
≡↑stroke risk
I B
↑hs-CRP →→? Statin IIb B
Annual influenza vaccination IIa B
HIV?
Aspirin for Primary Stroke Prevention
Aspirin in CV risk 6%-10% I A
Aspirin not useful in low risk patients III A
Aspirin not useful in DM or DM+
asymptomatic PAD in the absence of
other established CVD
III B
Assessing the Risk of First Stroke
Stroke risk assesment I A
Stroke risk-assessment tools
Framingham stroke profile
IIa B
Stroke or TIA survivors have an increased risk of a subsequent stroke
Recurrent strokes are more likely than initial strokes to result in disability and death
~ 20%-40% of strokes are preceded by a TIA or non disabling stroke
Rothwell et al. Lancet Neurol 2006; 5: 323-331
Evaluate the Event
Implement Interventions Initiate Medications
Modify Stroke Risk Factor: Continuous Monitoring
TIA Stroke Risk Assessment
High Risk
1. Symptom onset within the last 48 hours with any one of the following :
Motor deficit lasting more than 5 minutes
Speech deficit lasting more than 5 minutes
ABCD2 score ≥ 4
2. Atrial fibrillation with TIA
TIA Stroke Risk Assessment Medium Risk
Symptom onset between 48 hours and 7 days with any one of the following :
Motor deficit lasting more than 5 minutes
Speech deficit lasting more than 5 minutes
ABCD2 score ≥ 4
Low Risk 1. Symptom onset > 7 days
2. Symptom onset ≤ 7 days without the presence of high risk symptoms Speech deficit, motor deficit, ABCD2 score ≥ 4, atrial fibrillation with TIA
› CT or MRI
Rule out mimics, identify stroke type
› Carotid Imaging (carotid duplex, CTA or MRA)
Identify stenosis
› ECG
? Cardiac cause - afib
Holter monitor
› Echocardiogram
If suspect cardiac cause
› Labs - CBC, UECr, RBS, PTT, INR, fasting lipids
63 Year old male, DM, Hypertension, non smoker, teetotaler
4 months ago developed sudden onset right hemiparesis, initial power 2/5, Improved to 4/5. Speech normal
Preceded by episodic right sided numbness and mild weakness that usually resolved
Referred Re: one week of worsening right hemiparesis
On Insulin, Amlodipine, Aspirin
Carotid Endarterectomy vs Medical Rx
Trial Mean Follow-up Surgical Arm* Medical Arm*
ECST
3 y
2.8%
16.8%
NASCET
2.7 y
9%
26%
VACS
11.9 mo
7.9%
25.6%
ECST indicates European Carotid Surgery Trial; NASCET, North American Symptomatic Carotid Endarterectomy Trial; and
VACS, Veterans Affairs Cooperative Study Program.
*Risk of fatal or nonfatal ipsilateral stroke.
CREST: Hazard Ratio for CAS vs CEA
Periprocedural HR
(95% CI)
4-Year Study Period
HR
(95% CI)
MI 0.45 (0.18-1.11) ---
Any periprocedural
stroke or postprocedural
ipsilateral stroke 1.74 (1.02-2.98) 1.29 (0.84-1.98)
Any periprocedural
stroke, death, or
postprocedural
ipsilateral stroke
1.89 (1.11-3.21) 1.37 (0.90-2.09)
Any periprocedural
stroke, MI, death, or
postprocedural
ipsilateral stroke
1.26 (0.81-1.96) 1.08 (0.74-1.59)
Risk Factor – Symptomatic Extracranial Carotid
Disease
Recommendations
Class/Level of
Evidence
TIA or ischemic stroke within 6 months and ipsilateral
severe carotid artery stenosis, CEA if perioperative
morbidity and mortality risk is estimated to be <6%.
Class I; A
Ipsilateral moderate carotid stenosis, CEA depending on
patient-specific factors if the perioperative morbidity and
mortality risk is estimated to be <6%.
Class I; B
Stenosis <50%, no indication for carotid revascularization Class III; A
Recommendations for Interventional Approaches to Patients
With Stroke Caused by Large-Artery Atherosclerotic Disease
Risk Factor – Symptomatic Extracranial
Carotid Disease
Recommendations
CEA surgery within 2 weeks reasonable if there
are no contraindications to early
revascularization.
Class IIa; B
CAS an alternative to CEA for symptomatic
patients at average or low risk of
complications of endovascular intervention.
Class I; B
82 Year old male, DM, non smoker, teetotaler
2 days of severe dizziness+ Gait ataxia. Tendency to fall right side
Clinically cerebellar dysfunction
MRI Brain→Right cerebellar infarct
On Metformin, Aspirin, Cinnarizine
82 Year old male, DM, non smoker, teetotaler
2 days of severe vertigo+ Gait ataxia. Tendency to fall right side
Clinically cerebellar dysfunction
MRI Brain→Right cerebellar infarct
On Metformin, Aspirin, Cinnarizine
Extracranial Vertebrobasilar Disease
• Persons with occlusive disease of the proximal and cervical portions of the vertebral artery (VA) are at relatively high risk for posterior or vertebrobasilar circulation ischemia.
• Symptomatic VA stenosis carries a high recurrent risk in the first 7 days after symptoms onset than patients with recently symptomatic carotid stenosis.
• ? Medical therapy
• ? Role of invasive treatment
Intracranial Atherosclerosis
High risk of subsequent stroke.
The WASID trial
Aspirin >>>Warfarin
BP, cholesterol control
?Angioplasty+/- Stenting
EC/IC bypass NOT recommended
Atrial Fibrillation and Stroke
• Persistent and paroxysmal Afib are potent risk factors for first and recurrent stroke
• Subclinical atrial fibrillation
• VKA anticoagulation, Dabigatran, Rivaroxaban
• CHADS2VASc
Risk Factor – Atrial Fibrillation
Ischemic stroke or TIA with paroxysmal
(intermittent) or permanent AF → VKA
Dabigatran
Rivaroxaban
Class I A
Unable to take oral anticoagulants→ Aspirin
Clopidogrel + Aspirin risk of bleeding ≡
warfarin
Class I A
Class III B
AF at high risk for stroke, temporary interruption
of oral anticoagulation →→ LMWH
Class IIa C
Recommendations for Patients With
Cardioembolic Stroke Types
Acute MI and LV Thrombus
Risk Factor – Acute MI and LV
Thrombus
Class/Lev
el of
Evidence
Ischemic stroke or TIA →→oral
anticoagulation (target INR 2.5;
range 2.0 to 3.0) >=3 months.
Class I B
Risk Factor – Cardiomyopathy Class/Level
of
Evidence
Prior stroke/TIA in sinus rhythm with
cardiomyopathy (LVEF 35%), ?the benefit of
warfarin
Class IIb B
Warfarin, Aspirin (81 mg daily), clopidogrel (75
mg daily), or Aspirin (25 mg twice daily) plus ER
dipyridamole (200 mg twice daily)
Class IIb B
Recommendations for Patients With Cardioembolic Stroke Types
Risk Factor – Native Valvular Heart Disease Class/Level
of Evidence
Rheumatic mitral valve disease+/- AF →→ long-term
warfarin
Class IIa C
Antiplatelet agents should not be routinely added to
warfarin.
Class III C
Native aortic or nonrheumatic mitral valve disease -
AF, antiplatelet therapy
Class IIb C
Mitral annular calcification →→ antiplatelet therapy Class IIb C
MVP →→ long-term antiplatelet therapy may be
considered.
Class IIb C
Recommendations for Patients With Cardioembolic Stroke Types
Risk Factor – Prosthetic Heart Valves Class/Level of
Evidence
Mechanical prosthetic heart valves →→
warfarin INR target of 3.0 (range, 2.5 to 3.5).
Class I; B
Mechanical prosthetic heart valves with
event despite adequate therapy with oral
anticoagulants→→→add aspirin 75-100
mg/d
Class IIa; B
Bioprosthetic heart valves with no other
source of thromboembolism ?Warfarin
Class IIb; C
Recommendations for Patients With Cardioembolic
Stroke Types
Class/Level of Evidence
Aspirin (50-325 mg/d)
Aspirin 25 mg + ER Dipyridamole 200 mg BD
Clopidogrel 75 mg
ASA + Clopidogrel
Class IA-IIB
Recommendations for Antithrombotic Therapy for Noncardioembolic Stroke or TIA
Pregnancy
PFO
Sickle Cell Disease
Cerebral Venous Sinus Thrombosis
Post-menopausal HRT
Hyperhomocysteinemia
Inherited Thrombophilias
APL syndrome
Stroke Patients With Other Specific Conditions